{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:57:43Z","timestamp":1792202263427,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T00:00:00Z","timestamp":1603152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010091","name":"International Foundation for CDKL5 Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010091","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1117105"],"award-info":[{"award-number":["APP1117105"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Characterized by early\u2010onset seizures, global developmental delay and severe motor deficits, CDKL5 deficiency disorder is caused by pathogenic variants in the cyclin\u2010dependent kinase\u2010like 5 gene. Previous efforts to investigate genotype\u2010phenotype relationships have been limited due to small numbers of recurrent mutations and small cohort sizes. Using data from the International CDKL5 Disorder Database we examined genotype\u2010phenotype relationships for 13 recurrent\n                    <jats:italic>CDKL5<\/jats:italic>\n                    variants and the previously analyzed historic variant groupings. We have applied the CDKL5 Developmental Score (CDS) and an adapted version of the CDKL5 Clinical Severity Assessment (CCSA), to grade the severity of phenotype and developmental outcomes for 285 individuals with\n                    <jats:italic>CDKL5<\/jats:italic>\n                    variants. Comparisons of adapted CCSA and CDS between recurrent variants and variant groups were performed using multiple linear regression adjusting for age and sex. Individuals with the missense variant, p.Arg178Trp, had the highest mean adapted CCSA and lowest mean developmental scores. Other variants producing severe phenotypes included p.Arg559* and p.Arg178Gln. Variants producing milder phenotypes included p.Arg134*, p.Arg550*, and p.Glu55Argfs*20. There are observed differences in phenotype severity and developmental outcomes for individuals with different CDKL5 variants. However, the historic variant groupings did not seem to reflect differences in phenotype severity or developmental outcomes as clearly as analyzed by individual variants.\n                  <\/jats:p>","DOI":"10.1111\/cge.13862","type":"journal-article","created":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T22:52:47Z","timestamp":1602543167000},"page":"157-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Exploring genotype\u2010phenotype relationships in the\n                    <scp>CDKL5<\/scp>\n                    deficiency disorder using an international dataset"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1301-7317","authenticated-orcid":false,"given":"Conor I.","family":"MacKay","sequence":"first","affiliation":[{"name":"Telethon Kids Institute The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kingsley","family":"Wong","sequence":"additional","affiliation":[{"name":"Telethon Kids Institute The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott T.","family":"Demarest","sequence":"additional","affiliation":[{"name":"Children's Hospital Colorado  Aurora Colorado USA"},{"name":"Departments of Pediatrics and Neurology University of Colorado at Denver  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim A.","family":"Benke","sequence":"additional","affiliation":[{"name":"Children's Hospital Colorado  Aurora Colorado USA"},{"name":"Departments of Pediatrics, Pharmacology, Neurology and Otolaryngology University of Colorado at Denver  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-9037","authenticated-orcid":false,"given":"Jenny","family":"Downs","sequence":"additional","affiliation":[{"name":"Telethon Kids Institute The University of Western Australia  Perth Western Australia Australia"},{"name":"School of Physiotherapy and Exercise Science Curtin University  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6405-5834","authenticated-orcid":false,"given":"Helen","family":"Leonard","sequence":"additional","affiliation":[{"name":"Telethon Kids Institute The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/375538"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.156"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/426462"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003352"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-7-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0418-y"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2019.02.015"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16285"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01520.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2010.03889.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812451497"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-13-68"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35401"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37851"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606325200"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rasd.2008.12.004"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000304752.50773.ec"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2019.03.017"},{"key":"e_1_2_8_21_1","volume-title":"Stata 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JB","year":"2015","journal-title":"Neurology"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn197"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.114"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-15-24"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01194.x"},{"issue":"3","key":"e_1_2_8_30_1","first-page":"137","article-title":"CDKL5\u2010related disorders: from clinical description to molecular genetics","volume":"2","author":"Bahi\u2010Buisson N","year":"2012","journal-title":"Mol 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